scholarly journals Regenerative Potential of DPSCs and Revascularization: Direct, Paracrine or Autocrine Effect?

2021 ◽  
Author(s):  
Vincenzo Mattei ◽  
Stefano Martellucci ◽  
Fanny Pulcini ◽  
Francesca Santilli ◽  
Maurizio Sorice ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Tissue Regeneration ◽  
Dental Pulp ◽  
Perivascular Cells ◽  
Reciprocal Interactions ◽  
Angiogenesis Process ◽  
Mechanism Of Interaction

AbstractA new source of mesenchymal stem cells has recently been discovered, the so-called dental pulp derived stem cells (DPSCs) which therefore could represent potentially tools for regenerative medicine. DPSC originate from the neural crest and are physiologically involved in dentin homeostasis; moreover, they contribute to bone remodeling and differentiation into several tissues including cartilage, bone, adipose and nervous tissues. DPSCs have also been shown to influence the angiogenesis process, for example through the release of secretory factors or by differentiating into vascular and/or perivascular cells. Angiogenesis, that has a pivotal role in tissue regeneration and repair, is defined as the formation of new vessels from preexisting vessels and is mediated by mutual and reciprocal interactions between endothelial cells and perivascular cells. It is also known that co-cultures of perivascular and endothelial cells (ECs) can form a vascular network in vitro and also in vivo. Since DPSCs seem to have characteristics similar to pericytes, understanding the possible mechanism of interaction between DPSCs and ECs during neo-angiogenesis is dramatically important for the development of advanced clinical application in the field of regeneration. Graphical abstract

Effects of In Vitro Osteogenic Induction on In Vivo Tissue Regeneration by Dental Pulp and Periodontal Ligament Stem Cells

2015 ◽  
Vol 41 (9) ◽  
pp. 1462-1468 ◽  
Author(s):  
Yoonsun Cha ◽  
Mijeong Jeon ◽  
Hyo-Seol Lee ◽  
Seunghye Kim ◽  
Seong-Oh Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tissue Regeneration ◽  
Dental Pulp ◽  
Periodontal Ligament ◽  
Periodontal Ligament Stem Cells ◽  
Osteogenic Induction

scholarly journals Exosomes Derived From Stem Cells From Apical Papilla Promote Craniofacial Soft Tissue Regeneration Through Enhancing Cdc42-Mediated Vascularization

2020 ◽  
Author(s):  
Yao Liu ◽  
Xueying Zhuang ◽  
Si Yu ◽  
Ning Yang ◽  
Jianhong Zeng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Endothelial Cells ◽  
Soft Tissue ◽  
Tissue Regeneration ◽  
Soft Tissue Regeneration ◽  
Apical Papilla ◽  
Craniofacial Tissue

Abstract Background: Reconstruction of complex critical-size defects (CSD) in craniofacial region is a major challenge, and the soft tissue regeneration is crucial in determining the therapeutic outcome of craniofacial CSD. Stem cells from apical papilla (SCAP) are neural crest-derived mesenchymal stem cells (MSCs) which are homologous to craniofacial tissue, and represent a promising source for craniofacial tissue regeneration. Exosomes, which contained compound bioactive contents, are the key factors of stem cell paracrine action. However, the roles of exosomes derived from SCAP (SCAP-Exo) in tissue regeneration are not fully understood. Here, we explored the effects and underlying mechanisms of SCAP-Exo on CSD in maxillofacial soft tissue.Methods: SCAP-Exo were isolated and identified by transmission electron microscopy and nanoparticle tracking analysis. The effects of SCAP-Exo on wound healing and vascularisation were detected by measuring wound area, histological and immunofluorescence analysis in the palate gingiva CSD of mice. Real-time live cell imaging and functional assays were used to assess the effects of SCAP-Exo on the biological functions of endothelial cells (ECs). Furthermore, the molecular mechanisms of SCAP-Exo mediated ECs angiogenesis in vitro was tested by immunofluorescence staining, Western blot and Pull-Down assays. Finally, in vivo experiments were carried out to verify whether SCAP-Exo could affect the vascularisation and wound healing through Cdc42.Results: We showed that SCAP-Exo promoted tissue regeneration of palatal gingiva CSD by enhancing vascularisation in the early phase in vivo, and also indicated SCAP-Exo improved the angiogenic capacity of endothelial cells (ECs) in vitro. Mechanistically, SCAP-Exo elevated cell migration by improving cytoskeletal reorganization of ECs via cell division cycle 42 (Cdc42) signalling. Furthermore, we revealed that SCAP-Exo transferred Cdc42 into the cytoplasm of ECs, and the Cdc42 protein could be reused directly by the recipient ECs, which resulted in the activation of Cdc42 dependent filopodia formation and elevation of cell migration of ECs.Conclusion: This study demonstrated that SCAP-Exo had a superior effect on angiogenesis and effectively promoted craniofacial soft tissue regeneration. These data provide a new option for SCAP-Exo to be used as a cell-free approach to optimize tissue regeneration in the clinic.

scholarly journals Bone marrow–derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature

Blood ◽  
2008 ◽  
Vol 111 (9) ◽  
pp. 4551-4558 ◽  
Author(s):  
Patrick Au ◽  
Joshua Tam ◽  
Dai Fukumura ◽  
Rakesh K. Jain
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Vascular Tissue ◽  
Vascular Tissue Engineering ◽  
Perivascular Cells ◽  
Perivascular Cell

Abstract Vascular tissue engineering requires a ready source of endothelial cells and perivascular cells. Here, we evaluated human bone marrow–derived mesenchymal stem cells (hMSCs) for use as vascular progenitor cells in tissue engineering and regenerative medicine. hMSCs expressed a panel of smooth muscle markers in vitro including the cardiac/smooth muscle–specific transcription coactivator, myocardin. Cell-cell contact between endothelial cells and hMSCs up-regulated the transcription of myocardin. hMSCs efficiently stabilized nascent blood vessels in vivo by functioning as perivascular precursor cells. The engineered blood vessels derived from human umbilical cord vein endothelial cells and hMSCs remained stable and functional for more than 130 days in vivo. On the other hand, we could not detect differentiation of hMSCs to endothelial cells in vitro, and hMSCs by themselves could not form conduit for blood flow in vivo. Similar to normal perivascular cells, hMSC-derived perivascular cells contracted in response to endothelin-1 in vivo. In conclusion, hMSCs are perivascular cell precursors and may serve as an attractive source of cells for use in vascular tissue engineering and for the study of perivascular cell differentiation.

scholarly journals Exosomes derived from stem cells from apical papilla promote craniofacial soft tissue regeneration through enhancing Cdc42-mediated vascularization

2020 ◽  
Author(s):  
Yao Liu ◽  
Xueying Zhuang ◽  
Si Yu ◽  
Ning Yang ◽  
Jianhong Zeng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Endothelial Cells ◽  
Soft Tissue ◽  
Tissue Regeneration ◽  
Soft Tissue Regeneration ◽  
Apical Papilla ◽  
Craniofacial Tissue

Abstract Background: Reconstruction of complex critical-size defects (CSD) in craniofacial region is a major challenge, and the soft tissue regeneration is crucial in determining the therapeutic outcome of craniofacial CSD. Stem cells from apical papilla (SCAP) are neural crest-derived mesenchymal stem cells (MSCs) which are homologous to craniofacial tissue, and represent a promising source for craniofacial tissue regeneration. Exosomes, which contained compound bioactive contents, are the key factors of stem cell paracrine action. However, the roles of exosomes derived from SCAP (SCAP-Exo) in tissue regeneration are not fully understood. Here, we explored the effects and underlying mechanisms of SCAP-Exo on CSD in maxillofacial soft tissue. Methods: SCAP-Exo were isolated and identified by transmission electron microscopy and nanoparticle tracking analysis. The effects of SCAP-Exo on wound healing and vascularisation were detected by measuring wound area, histological and immunofluorescence analysis in the palate gingiva CSD of mice. Real-time live cell imaging and functional assays were used to assess the effects of SCAP-Exo on the biological functions of endothelial cells (ECs). Furthermore, the molecular mechanisms of SCAP-Exo mediated ECs angiogenesis in vitro was tested by immunofluorescence staining, Western blot and Pull-Down assays. Finally, in vivo experiments were carried out to verify whether SCAP-Exo could affect the vascularisation and wound healing through Cdc42. Results: We showed that SCAP-Exo promoted tissue regeneration of palatal gingiva CSD by enhancing vascularisation in the early phase in vivo , and also indicated SCAP-Exo improved the angiogenic capacity of endothelial cells (ECs) in vitro . Mechanistically, SCAP-Exo elevated cell migration by improving cytoskeletal reorganization of ECs via cell division cycle 42 (Cdc42) signalling. Furthermore, we revealed that SCAP-Exo transferred Cdc42 into the cytoplasm of ECs, and the Cdc42 protein could be reused directly by the recipient ECs, which resulted in the activation of Cdc42 dependent filopodia formation and elevation of cell migration of ECs. Conclusion: This study demonstrated that SCAP-Exo had a superior effect on angiogenesis and effectively promoted craniofacial soft tissue regeneration. These data provide a new option for SCAP-Exo to be used as a cell-free approach to optimize tissue regeneration in the clinic.

P-EP013. Superior migration propensity of dental pulp stem cells in in vitro and in vivo models of excitotoxic neurodegeneration

2021 ◽  
Vol 132 (8) ◽  
pp. e82-e83
Author(s):  
Sivapriya Senthilkumar ◽  
Chaitra Venugopal ◽  
K. Shobha ◽  
Bindu M. Kutty ◽  
Anandh Dhanushkodi
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
In Vivo Models ◽  
Migration Propensity

Abstract 558: Microchanneled Polysaccharide Hydrogel Laden With Endothelial Cells and Mesenchymal Stem Cells With VEGF Facilitate Formation of Vascular Structures and Are Effective for Repairing Tissue Ischemia

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Sangho Lee ◽  
Min Kyung Lee ◽  
Hyunjoon Kong ◽  
Young-sup Yoon
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Survival ◽  
Vascular Structure ◽  
Hindlimb Ischemia ◽  
Alginate Hydrogel ◽  
Vessel Formation

Various hydrogels are used to create vascular structure in vitro or to improve cell engraftment to overcome low cell survival in vivo, a main hurdle for bare cell therapy Recently we developed a modified alginate hydrogel within which microchannels are aligned to guide the direction and spatial organization of loaded cells. We investigated whether these cell constructs in which HUVECs and human mesenchymal stem cells (hMSCs) are co-loaded in this novel microchanneled hydrogel facilitate formation of vessels in vitro and in vivo, and enhance recovery of hindlimb ischemia. We crafted a modified alginate hydrogel which has microchannels, incorporates a cell adhesion peptide RGD, and was encapsulated with VEGF. We then compared vascular structure formation between the HUVEC only (2 x 105 cells) group and the HUVEC plus hMSC group. In the HUVEC+hMSC group, we mixed HUVECs and hMSCs at the ratio of 3:1. For cell tracking, we labeled HUVECs with DiO, a green fluorescence dye. After loading cells into the microchannels of the hydrogel, these constructs were cultured for seven days and were examined by confocal microscopy. In the HUVEC only group, HUVECs stands as round shaped cells without forming tubular structures within the hydrogel. However, in the HUVEC+hMSC group, HUVECs were stretched out and connected with each other, and formed vessel-like structure following pre-designed microchannels. These results suggested that hMSCs play a critical role for vessel formation by HUVECs. We next determined their in vivo effects using a mouse hindlimb ischemia model. We found that engineered HUVEC+hMSC group showed significantly higher perfusion over 4 weeks compared to the engineered HUVEC only group or bare cell (HUVEC) group. Confocal microscopic analysis of harvested tissues showed more robust vessel formation within and outside of the cell constructs and longer term cell survival in HUVEC+hMSC group compared to the other groups. In conclusion, this novel microchanneled alginate hydrogel facilitates aligned vessel formation of endothelial cells when combined with MSCs. This vessel-embedded hydrogel constructs consisting of HUVECs and MSCs contribute to perfusable vessel formation, prolong cell survival in vivo, and are effective for recovering limb ischemia.

scholarly journals The Interplay of Dental Pulp Stem Cells and Endothelial Cells in an Injectable Peptide Hydrogel on Angiogenesis and Pulp Regeneration In Vivo

2015 ◽  
Vol 21 (3-4) ◽  
pp. 550-563 ◽  
Author(s):  
Waruna Lakmal Dissanayaka ◽  
Kenneth M. Hargreaves ◽  
Lijian Jin ◽  
Lakshman P. Samaranayake ◽  
Chengfei Zhang
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Pulp Regeneration ◽  
Peptide Hydrogel

scholarly journals Evaluation of Angiogenesis Assays

Biomedicines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 37 ◽  
Author(s):  
Zachary I. Stryker ◽  
Mehdi Rajabi ◽  
Paul J. Davis ◽  
Shaker A. Mousa
Keyword(s):  
Endothelial Cells ◽  
Tube Formation ◽  
Angiogenic Activity ◽  
In Vitro Methods ◽  
Current State ◽  
Angiogenesis Process ◽  
Pertinent Information ◽  
Exogenous Factors

Angiogenesis assays allow for the evaluation of pro- or anti-angiogenic activity of endogenous or exogenous factors (stimulus or inhibitors) through investigation of their pro-or anti- proliferative, migratory, and tube formation effects on endothelial cells. To model the process of angiogenesis and the effects of biomolecules on that process, both in vitro and in vivo methods are currently used. In general, in vitro methods monitor specific stages in the angiogenesis process and are used for early evaluations, while in vivo methods more accurately simulate the living microenvironment to provide more pertinent information. We review here the current state of angiogenesis assays as well as their mechanisms, advantages, and limitations.

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